The long-term goal of this proposal is to explore how the sarcolemma of cardiac cells links myocardial contractility to extracellular calcium and to define how selected pharmacolgical interventions and pathological perturbations alter this linkage. The immediate specific aims of the proposal are as follows: (1) to devise isolation schemes to obtain highly purified sarcolemma from canine ventricular tissue with high yield and to separate the vesicles into subgroups containing right-side out and inside out vesicles; (2) to test alternate hypotheses concerned with pathways for calcium efflux out of the myocardial cell (viz., sodium-calcium exchange versus an ATP-dependent calcium pump); and (3) to test the hypothesis that an electric-field induced redistribution of charges across the sarcolemma membrane alters the order of the lipid bilayer which, in turn, increases membrane permeability to calcium and to test the alternate hypothesis that field-induced displacements of calcium from the surface allows the bilayer to convert from an ordered to a fluid state which increases membrane permeability.